Schedule H

Oral

• Capsules: 75 mg, 110 mg, 150 mg (as dabigatran etexilate mesilate)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Prevention of Stroke and Systemic Embolism in Non-Valvular Atrial Fibrillation (NVAF)

Patient Category Dosing

Starting dose 150 mg twice daily (standard patients); 110 mg twice daily (age ≥75 years, CrCl 30–50 mL/min, or high bleeding risk)

Titration Not applicable — fixed-dose regimen

Usual maintenance dose 150 mg twice daily OR 110 mg twice daily based on clinical assessment

Maximum dose 150 mg twice daily

Clinical Selection Guide:

Age/Clinical Status Recommended Dose Key Considerations

<75 years with CrCl >50 mL/min 150 mg twice daily Preferred for stroke prevention efficacy

≥75 years 110 mg twice daily Increased bleeding risk with higher dose

CrCl 30–50 mL/min 110 mg twice daily Impaired drug clearance

High bleeding risk (any age) 110 mg twice daily Individualise based on bleeding vs stroke risk

Duration: Lifelong unless contraindication develops

1. Treatment of Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE)

Parameter Recommendation

Starting dose Parenteral anticoagulant (LMWH or unfractionated heparin) for 5–10 days FIRST

Titration Not applicable

Usual maintenance dose 150 mg twice daily after completion of parenteral phase

Maximum dose 150 mg twice daily

Key Clinical Notes:

• Dabigatran must NOT be initiated without prior parenteral anticoagulation

• Minimum treatment duration: 3 months

• Extended therapy individualised based on recurrence risk vs bleeding risk

• Consider 110 mg twice daily in patients ≥75 years or with CrCl 30–50 mL/min

1. Prevention of Recurrent DVT/PE (Extended Therapy)

Parameter Recommendation

Starting dose 150 mg twice daily (after completion of initial treatment course)

Titration Not applicable

Usual maintenance dose 150 mg twice daily; 110 mg twice daily if high bleeding risk

Maximum dose 150 mg twice daily

Duration: Individualised; reassess risk-benefit at regular intervals

Secondary Indications — Adults Only (Off-label)

Indication Dose Duration Notes Evidence Basis

Thromboprophylaxis in cancer-associated thrombosis 150 mg twice daily after initial LMWH (5–10 days) Specialist-determined OFF-LABEL — Specialist only; Higher bleeding risk in GI malignancies; LMWH generally preferred in active cancer HOKUSAI-VTE Cancer trial; International RCT data

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

NOT AVAILABLE in India

• No CDSCO approval for paediatric use currently exists

• No Indian guidelines support routine paediatric use

• Weight-based dosing regimens exist in international data (children ≥3 months for VTE treatment) but are not applicable to Indian practice

Secondary Indications — Paediatric (Off-label)

Not recommended in patients below 18 years in Indian practice

• No local approval or established safety data

• Use restricted to institutional clinical trial protocols under specialist supervision only

• LMWH remains preferred anticoagulant in paediatric population in India

CrCl (mL/min) Dose Recommendation

50 No adjustment required

30–50 110 mg twice daily; individualise based on bleeding risk

<30 Contraindicated

Haemodialysis Avoid use — Dabigatran is dialyzable but clinical experience insufficient; not recommended

Monitoring Note: Assess renal function at baseline and regularly thereafter (every 6 months in stable patients; more frequently in elderly or if decline suspected)

• Severe renal impairment (CrCl <30 mL/min)

• Active clinically significant bleeding

• Mechanical or bioprosthetic heart valves

• Hepatic disease associated with coagulopathy

• Known hypersensitivity to dabigatran etexilate or any excipient

• Concurrent use with systemic ketoconazole, itraconazole, cyclosporine, or dronedarone

• Lesions or conditions with significant risk of major bleeding (e.g., active GI ulcer, recent intracranial haemorrhage)

• Age ≥75 years (increased bleeding risk)

• CrCl 30–50 mL/min (requires dose reduction)

• Body weight <50 kg

• Recent major surgery or trauma

• History of GI bleeding or peptic ulcer disease

• Concomitant use of NSAIDs or antiplatelet agents

• Conditions predisposing to bleeding (e.g., inherited or acquired coagulation disorders)

• Rapid decline in renal function

• Risk of thromboembolism on abrupt discontinuation — bridge with alternative anticoagulant if necessary

• Bacterial endocarditis

Aspect Recommendation

Overall safety statement Not recommended; limited human data; animal studies indicate reproductive toxicity

Preferred alternatives in Indian obstetric practice LMWH (enoxaparin) is standard of care for anticoagulation during pregnancy

When it may be used Only if no alternative exists AND benefit clearly outweighs risk; under specialist supervision

What to monitor Maternal bleeding complications; fetal growth and wellbeing; consider switching to LMWH well before delivery

Aspect Recommendation

Compatible with breastfeeding Not recommended

Preferred alternatives LMWH (enoxaparin); warfarin (acceptable postpartum)

Expected drug levels in milk Unknown in humans; excreted in animal milk studies

What to monitor in infant Signs of bleeding, bruising, low platelet counts if inadvertent exposure occurs

Aspect Recommendation

Recommended starting dose 110 mg twice daily in patients ≥75 years

Need for slower titration Not applicable (fixed-dose regimen); initiate at lower dose

Extra risks Higher GI bleeding risk especially with 150 mg dose; declining renal function; increased fall risk; polypharmacy interactions

Monitoring: Renal function every 6 months or more frequently if clinically indicated

Interacting Drug Effect Recommendation

Ketoconazole (systemic) Strong P-gp inhibition → markedly increased dabigatran levels Contraindicated

Itraconazole (systemic) Strong P-gp inhibition Contraindicated

Cyclosporine Strong P-gp inhibition Contraindicated

Dronedarone Strong P-gp inhibition Contraindicated

Rifampicin Strong P-gp induction → significantly reduced dabigatran efficacy Avoid combination

Other anticoagulants (heparin, LMWH, warfarin) Additive anticoagulant effect Avoid concurrent use except during switching protocols

Thrombolytics Markedly increased bleeding risk Avoid combination

Interacting Drug Effect Recommendation

Amiodarone Moderate P-gp inhibition → increased dabigatran levels (12–60%) Consider 110 mg twice daily; monitor for bleeding

Verapamil Moderate P-gp inhibition Administer dabigatran 2 hours before verapamil; consider dose reduction

Clarithromycin Moderate P-gp inhibition Monitor for bleeding signs

Quinidine Moderate P-gp inhibition Use with caution; monitor

Carbamazepine/Phenytoin P-gp induction → reduced dabigatran levels Monitor for reduced efficacy

NSAIDs Increased bleeding risk (pharmacodynamic) Use with caution; avoid long-term concurrent use

Antiplatelet agents (aspirin, clopidogrel) Increased bleeding risk Use only when clearly indicated; monitor closely

HIV protease inhibitors Variable P-gp inhibition Avoid in renal impairment; use with caution otherwise

• Dyspepsia (most frequent cause of discontinuation)

• Gastritis-like symptoms

• Nausea

• Abdominal discomfort

• Minor bleeding (gingival, epistaxis, bruising)

• Diarrhoea

Adverse Effect Clinical Notes

Major GI haemorrhage More common than with warfarin; may require transfusion or intervention

Intracranial haemorrhage Lower incidence than warfarin but potentially fatal

Life-threatening bleeding Reversal agent idarucizumab (5 g IV) available in India

Anaphylaxis/angioedema Rare; discontinue immediately

Hepatic enzyme elevation Monitor LFTs; discontinue if significant

Acute kidney injury Rare; usually associated with severe bleeding

After initiation (2–4 weeks) Renal function (especially in elderly); clinical assessment for bleeding

Long-term Renal function every 6–12 months (more frequent if baseline impairment or age ≥75 years); haemoglobin at each follow-up; clinical bleeding assessment

Special situations aPTT or thrombin time (TT) only in suspected overdose or bleeding — not for routine monitoring

• Pradaxa (Boehringer Ingelheim) — Innovator brand

• Dabigo (Lupin)

• Dabinex (Macleods)

• Dabiwar (Zydus)

• Dabitra (Torrent)

• Additional generic brands available

Strength Approximate Price per Capsule

Note: Not currently under NLEM/NPPA price control

• Mandatory parenteral lead-in: Never initiate dabigatran for acute DVT/PE without 5–10 days of parenteral anticoagulation first

• Dyspepsia management: Consider PPI co-prescription to reduce GI-related discontinuation rates

• Strict adherence required: Emphasise twice-daily dosing at 12-hour intervals; short half-life means missed doses significantly increase thrombotic risk

• Capsule handling: Must be swallowed whole; do not open, crush, or chew — affects drug release

• Reversal availability: Ensure idarucizumab (Praxbind 5 g IV) is accessible in hospital for emergency bleeding

• Switching protocols: When switching from warfarin, start dabigatran when INR <2.0; when switching to warfarin, overlap based on CrCl (refer to institutional protocols)

• Perioperative management: Discontinue 24–48 hours before elective surgery (longer if CrCl <50 mL/min or high bleeding risk procedure)

anticoagulant; direct thrombin inhibitor; NVAF; atrial fibrillation; DVT; PE; venous thromboembolism; renal-adjustment; bleeding-risk; elderly-caution; pregnancy-avoid; India

RxIndia v1.0 — 07 Jun 2025

• CDSCO (Central Drugs Standard Control Organisation)

• Indian Pharmacopoeia (IP)

• AIIMS Drug Formulary

• API Textbook of Medicine

• NLEM 2022 (National List of Essential Medicines)

• Harrison's Principles of Internal Medicine

• ICMR Anticoagulation Guidelines (2023)

• Institutional protocols (AIIMS, CMC Vellore)

• RE-LY Trial (NVAF efficacy data)

• RE-COVER Trial (VTE treatment data)

• HOKUSAI-VTE Cancer Trial (off-label use evidence)